长期应用双膦酸盐类药物对老年性骨质疏松骨折愈合过程的影响

The effect of long-term use of bisphosphonates on fracture healing in elderly people with osteoporosis

目的探讨长期应用双膦酸盐类药物(阿仑膦酸钠)治疗老年性骨质疏松症所引起的骨质疏松骨折的可行性以及长期应用双膦酸盐类药物在骨质疏松骨折愈合过程中对于骨组织的影响,为临床正确应用抗骨吸收药物治疗原发性骨质疏松症提供科学理论根据。方法选择90只12月龄雌性SD大鼠,常规饲养至15月龄左右。每组于骨折造模前2周以及骨折造模后并开始给药后的2周、4周、8周、12周5个时间点,进行X线、组织形态、骨代谢生化标志物以及micro-CT的检测。结果 X线:实验组A早期有明显的梭形外骨痂,但12周未愈合。组织形态学:实验组A早期见大量软骨细胞,愈合晚期虽有改建后成熟骨小梁和新生血管,但骨折处未愈合。骨代谢生化标志物:BAP:实验组A于12周的成骨活性均低于实验组B和实验组C;CTX-1:实验组A于8周后其水平逐渐增高。Micro-CT:实验组A的骨小梁厚度、骨小梁数量减少;骨小梁分离度增加。(统计数据均利用SPSS16.0进行统计分析,P<0.05)。结论长期应用双膦酸盐药物治疗老年性骨质疏松引起的骨折会导致骨折断端愈合延迟甚至不愈合。

Objective To test the feasibility and the effect of long-term use of bisphosphonates on osteoporotic fractures and the healing process in the elderly people with osteoporosis,in order to provide a theoretical foundation for clinic antiresorptive therapy of primary osteoporosis.Methods Ninety 12-month-old female SD rats were selected and bred routinely for 15 months.X-ray scanning,histomorphology,bone metabolism biomarkers,and miscro-CT were conducted on 2 weeks before the model establishment,and on 2,4,8,and 12 weeks after the drug administration.Results X-ray： the spindle and bony callus appeared at the early stage in Group A.However the fracture was not healed in 12 weeks.Histomorphology： chondrocytes could be seen at early stage,and at advanced stage reconstruction and mature bone trabecular and neovessels were found but the fracture was not healed in Group A.Bone biomarkers： BAP： osteoblast activity was the lowest in Group A compared to Group B and C.CTX-1： it gradually increased in Group A in 8 weeks.Micro-CT： trabecular thickness and trabecular numbers decreased in Group A,but trabecular resolution increased.（Data were analyzed using SPSS 16.0,P0.05）.Conclusion The long-term application of bisphosphonates in senile osteoporosis may lead to delayed healing or even disunion of the fractures.